Map’s overview

Rheumatoid Arthritis (RA) concept map zoom out pharmacotherapy
Rheumatoid Arthritis (RA) Concept Map

Definition

Rheumatoid Arthritis is a chronic inflammatory autoimmune disease that involves the joints and may cause systemic manifestations.

Etiology

It is an autoimmune disease with unknown causes and contributing factors (genetic & environmental factors). Environmental factors like viral infections and cigarette smoking; trigger and maintain joint inflammation.

Epidemiology

  • Prevalence; 1% worldwide
  • Gender; Women:Men = 3:1 (after 50 years old, gender difference is less marked)
  • Age; peaks at 35-45 years old, although it can occur at any age – when it occurs in childhood, it is called “Juvenile Idiopathic Arthritis”
  • Limitations of activities:     * 33% have major activities limited     * 29% cannot perform major activities

Pathophysiology

Rheumatoid arthritis pathophysiology is shown in the map in the form of a cascade process that starts with an “Autoimmune Reaction” and ends with “Joint Destruction.”

rheumatoid_arthritis_definition_etiology_pathophysiology_zoom_out_pharmacotherapy-1
Etiology and Pathophysiology of Rheumatoid Arthritis

Clinical Presentation

Nonspecific signs & symptoms (for weeks/months): fever, malaise, arthralgias, and weakness.

Specific signs and symptoms that take weeks to months to appear.

Joint symptoms are characteristically symmetric, including: 

  • Stiffness lasts > 60 minutes after rising in the morning but may occur after any prolonged inactivity (called gelling).-
  • Erythema, warmth, swelling, and limitation of motion.

Joints involved in rheumatoid arthritis

  • The most common joints involved are; Wrists, feet (MTP), and the index (2nd) and middle (3rd) metacarpophalangeal (MCP) joints
  • Other joints include; Proximal interphalangeal (PIP) joints, shoulders, elbows, hips, knees, and ankles.
  • Any joint, except the distal interphalangeal (DIP) joints.

Irreversible joint deformities that may occur due to disease progression

  1.  Ulnar deviation of the fingers
  2. Boutonniere Deformity (hyperextension of the DIP & flexion of the PIP joint)
  3. Swan Neck Deformity (hyperextension of the PIP & flexion of the DIP joint)
  4. Hammer toe deformity

Progression

The disease progresses most rapidly during the first 6 years, particularly the first year; 80% of patients develop some permanent joint abnormalities within 10 years.

Extra-articular Manifestations

Most of rheumatoid arthritis extra-articular manifestations are collected in this image:

extra-articular_manifestations_rheumatoid_arthritis_zoom_out_pharmacotherapy
Rheumatoid arthritis extra-articular manifestations

Diagnosis

This part of the map includes History and Examination, Laboratory tests, Radiographic test (x-ray), ACR Rheumatoid Arthritis Diagnostic Criteria (2010). In addition, a comparison between rheumatoid arthritis and osteoarthritis is included.

rheumatoid_arthritis_vs_osteoarthritis_comparison_zoom_out_pharmacotherapy
Rheumatoid Arthritis vs Osteoarthritis

Treatment

Medications to Reduce Pain and Inflammation

1) Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

  • e.g., ibuprofen, naproxen, ketoprofen, piroxicam, and diclofenac.
  • adjunctive therapy.
  • treat symptoms and decrease inflammation but do not affect disease progression.
  • dose can be decreased or discontinued with successful Disease-modifying antirheumatic drugs (DMARDs) therapy.
  • adverse effects: GI toxicity, headache, confusion, and other CNS symptoms, increased BP, worsening of hypertension, edema, and decreased platelet function. NSAIDs increase cardiovascular risk. 
  • Non-steroidal anti-inflammatory drug drugs mechanism of action is shown in this diagram:
Non-steroidal-Anti-inflammatory-Drugs-Mechanism-of-Action-zoom-out-pharmacotherapy
Non-steroidal Anti-inflammatory Drugs – Mechanism of Action

2) COX-2 inhibitor (only celecoxib)

See the map. 

3) Low-dose systemic corticosteroids (CS)

  • adjunctive therapy       
  • decrease inflammation and other symptoms rapidly and efficiently 
  • slow bone erosion
When to use low-dose systemic CS in RA?
  • In early RA, low-dose oral prednisone (<10 mg/day) in combination with DMARDs for up to 6 months, as symptomatic effects ↓ with time 
  • In established RA, CS may be used as ‘bridging’ therapy when DMARDs are initiated, and should be withdrawn once DMARDs have controlled the disease
  • May be used for severe joint or systemic manifestations of RA (eg, vasculitis, pleurisy, pericarditis)
Contraindications
  • Relative contraindications include PUD, HTN, untreated infections, DM, and glaucoma 
  • The risk of latent TB should be considered before CS therapy is begun

4) Intraarticular depot corticosteroids

  • Temporarily control severe monarticular or even oligoarticular symptoms.
  • Triamcinolone hexacetonide may suppress inflammation for the longest time.
  • Triamcinolone acetonide and methylprednisolone acetate are also effective.
  • No single joint should be injected with a corticosteroid more than 3 to 4 times a year, as too-frequent injections may accelerate joint destruction.
  • Because injectable corticosteroid esters are crystalline, local inflammation transiently increases within a few hours in < 2% of patients receiving injections.
  • Although infection occurs in only < 1:40,000 patients, it must be considered if pain occurs > 24 h after injection.

Medications to Prevent Disease Progression & Loss of Joint Function

1) Disease-modifying antirheumatic drugs (DMARDs)

Also called “nonbiologic DMARDs,” include: methotrexate (MTX), hydroxychloroquine (HCQ), azathioprine (AZA), sulfasalazine (SSZ), and leflunomide. Other available but rarely used DMARDs include minocycline, azathioprine, cyclosporine, and tacrolimus.

  • Early treatment of RA (< 6 months after the onset of symptoms) with DMARDs retard disease progression more efficiently and induce more remissions.
  • Until the full action of DMARDs takes effect, anti-inflammatory or analgesic medications may be required as bridging therapy to reduce pain and swelling.
  • They differ from each other chemically and pharmacologically. 
  • Patients should be informed about the risks of DMARDs and monitored closely for evidence of toxicity.
  • Combinations of DMARDs may be more effective than single drugs. Also, combining a DMARD with another drug, such as methotrexate plus a TNF-α antagonist or an IL-1 receptor antagonist or a rapidly tapered corticosteroid, may be more effective than using DMARDs alone. 

A comparison between DMARDs is available in the map. The comparison is showing: mechanisms of actions, indications, doses, adverse effects, monitoring parameters, and contraindications.

DMARDs_comparison_zoom_out_pharmacotherapy
Disease Modifying Anti-Rheumatic Drugs (DMARDs) – Table Comparison

2) Biologic agents

  • Also called “biologic DMARDs.”
  • They are not given in combination with each other due to increased frequency of infections.
  • Approved by the FDA to treat moderate to severe RA not responded to an one or more of the traditional DMARDs.
  • They may be used alone, but are often in combination with other DMARDs, to increase the efficacy and decrease AE.
  • Start biologic agents while patients remain on NSAID and/or corticosteroid.

A comparison between the biologic agents is available in the map. The comparison is showing: mechanisms of actions, indications, doses, onset of action, adverse effects, contraindications, and warnings/cautions.

Biologic_agents_rheumatoid_arthritis_zoom_out_pharmacotherapy.jpg
Biologic DMARDs – Table Comparison

3) Other immunomodulatory, cytotoxic, and immunosuppressive drugs

e.g., Azathioprine, and cyclosporin A.  Rarely cyclophosphamide and d-Penicillamine.

  • Efficacy is similar to DMARDs but more toxic. 
  • Used in case of treatment failure with DMARDs or to decrease the need for CSs.
  • Used infrequently unless there are extra-articular complications. 

And here is a comparison between them:

immunomodulatory_cytotoxic_immunosuppressive_drugs_rheumatoid_arthritis_zoom_out_pharmacotherapy
Other immunomodulatory, cytotoxic, and immunosuppressive drugs – Table Comparison

Order the map

You can order the Rheumatoid Arthritis (RA) concept map in any of the following forms according to your preference. Our maps are comprehensive in a way that can benefit both students and clinicians.

This map is available in two forms;
1. Printable version.
2. Whole map version.

Check them out below to know the difference, so that you can choose what is suitable for you. And please feel free to leave your feedback, comments, or questions in the comments section below.

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